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Toxicogenomics in biomarker discovery

Marc F Decristofaro1, Kellye K Daniels

  • 1Biomarker Development, Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA.

Methods in Molecular Biology (Clifton, N.J.)
|May 2, 2008
PubMed

Insights

Toxicogenomics, using gene expression profiling, aids in predicting compound toxicity and identifying biomarkers. This review explores methods for discovering toxicity biomarkers through gene expression analysis.

Area of Science:

  • Toxicology
  • Toxicogenomics
  • Gene Expression Profiling

Background:

  • Toxicogenomics utilizes genome-scale mRNA expression profiling to assess adverse xenobiotic exposure.
  • It is explored for compound triage, toxicity mechanism elucidation, and biomarker identification.
  • Current methods for toxicity prediction and mechanism discovery exist, but biomarker discovery lacks clear protocols.

Purpose of the Study:

  • To broadly discuss the issues and utility of applying toxicogenomics to biomarker discovery.
  • To highlight the potential of gene expression technologies in identifying toxicity biomarkers.
  • To review existing and potential approaches for toxicogenomic biomarker discovery.

Main Methods:

  • Analysis of large gene expression profile databases with in silico mining for differentially expressed genes.
  • Examination of preclinical study gene expression data to identify genes correlating with or preceding pathology.
  • Direct gene expression profiling on blood samples from preclinical studies or clinical trials for noninvasive biomarker discovery.

Main Results:

  • Toxicogenomics offers multiple avenues for biomarker discovery, including database mining and analysis of preclinical/clinical data.
  • Identification of coincident and leading biomarkers is possible through gene expression analysis.
  • Noninvasive biomarker discovery is feasible via gene expression profiling of blood samples.

Conclusions:

  • Toxicogenomics presents a powerful approach for advancing toxicity testing and drug development.
  • Standardized methods for toxicogenomic biomarker discovery are needed.
  • Further research is warranted to fully leverage toxicogenomics for identifying predictive and diagnostic biomarkers.

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